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SHOULD BIOMARKERS REFLECT study was reported to be predictive of tumor relapse 9-12
INTERVENTION? months before the clinical and radiological evidence of
disease recurrence. [48] In a recent paper, CgA was an early
CgA has been used in gastroenteric NETs as a predictive predictor of recurrence 6 months before radiological
biomarker to identify patients most likely to have progression in metastatic NETs. [49] A reduction of > 80%
durable responses to long acting somatostatin analogue
therapy. [47] Further, early decreases in CgA after in CgA after cytoreductive surgery was shown to predict
somatostatin analogues plus everolimus was predictive disease control [50] and reduction of CgA was observed
[51]
of early response in pNET patients. [34] Increases in CgA after successful peptide receptor radionuclide therapy
levels after radical surgery in a large Italian observational and liver transplantation. [52]
Table 3: Pitfalls and bottlenecks and possible remedies for circulating u-5HIAA
Pitfalls and Possible causes Remidies suggested
bottleneck
High u-5HIAA Urinary collection Give some written information how to collect 24 h urine and to conserve. If result is
in patient with not correct doubtful and crucial for diagnostic and therapeutic choose repeat
suspected or
known NETs Intraindividual Perform two consecutive 24-h urine collections and take mean value of these two
Variation especially when collection required for diagnosis or when crucial for terapeutic choose
Recommend only certificated laboratories with high quality control certification
Doubtful in accuracy
determination
Keep in mind others pathological causes of elevated u-5HIAA as coeliac and Whipple’s
disease, intestinal stasis and cystic fibrosis
Others disease
Exclude from the diet from 72 h preceding and during urine collection
Tryptophan/ plums, pineapples, bananas, eggplants, tomatoes, avocados, walnuts, avocados, kiwi,
serotonin-riche food pecans, coffee, tea, cocoa, chocolate, vanilla, sweets and cookies
consumption
Keep in mind possible drugs interference. Stop if not contraindicated.
Drugs interference u-5HIAA levels were increased during Acetaminophene, naproxen, coumaric acid,
phenacetin, diazepam, ephedrine, glyceryl guaiacolate, methocarbamol, reserpine,
cisplatin, fluorouracil, melphalan, rauwolfia

Give some written instruction on drugs and food restriction and report all drugs in
medical records

Low u-5HIAA Urinary collection The same as for high levels
in patients with not correct
known or highly Intraindividual Keep in mind possible drugs interference. Stop if not contraindicated. U-5HIAA
suspected NETs variation levels were reduced during Chlorpromazine, heparin, imipramine, isoniazid,
levodopa, monoamine oxidase inhibitors, methenamine, methyldopa, phenothiazines,
Doubtful in promethazine, tricyclic antidepressants, chlorophenylalanine, corticotrophin, guanfacine,
accuracy imipramine, isocarboxazid, isoniazid, levodopa, MAO inhibitors, moclobemide,
determination acetylsalicylic acid, streptozotocina uses

Drugs interference Ethanol reduce u-5HIAA

Alcohol addiction SSA is known to decrease u-5HIAA. Assays for diagnostic purposes should be made in
patients not on somatostatin analogues therapy
Possible inhibitory
roles of SSA In the follow up setting urinary samples need to be collected on stable or comparable
SSA doses

Report in patient medical record type of somatostatin analogue and frequency of
administration and eventually subcutaneous octreotide performed in the last 24 h before
determination
NETs: neuroendocrine tumors; PPIs: proton pump inhibitors; SSA: somatostatin analogues; u-5HIAA: urinary 5-Hydroxy-indolacetic acid

Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ August 31, 2016 ¦ 353